About

Allen C. Gao, M.D., Ph.D., is a professor and the Director of Research in the Department of Urologic Surgery at UC Davis Health. His research primarily focuses on understanding the molecular changes associated with the progression of prostate cancer, with the goal of identifying diagnostic markers and therapeutic targets to halt the advancement of late-stage prostate cancer. Dr. Gao's work involves investigating molecular pathways and signaling mechanisms relevant to urologic oncology, particularly prostate cancer, and developing targeted treatments. He earned his M.D. from Sichuan Medical College in China and completed a Ph.D. in Molecular Biology at the University of Texas MD Anderson Cancer Center. His postdoctoral training includes a fellowship in Urology and Oncology at Johns Hopkins University. Dr. Gao has held leadership roles such as President of the Society for Basic Urologic Research and is a Senior Research Career Scientist at the Department of Veterans Affairs. He holds the Ralph deVere White endowed Professorship in Urologic Oncology Research at UC Davis. His contributions include advancing understanding of molecular mechanisms in prostate cancer and developing novel therapeutic strategies.

Research topics

• Cancer research
• Medicine
• Internal medicine
• Biology
• Oncology
• Cell biology
• Endocrinology
• Pharmacology
• Biochemistry
• Chemistry
• Genetics
• Urology

Selected publications

• Figure S1 from PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells

  2026-03-16

  articleOpen accessSenior author

  <p>supplementary figure</p>

  PublisherDOI

• Characterizing Response to PARP Inhibitor Treatment Combinations in Advanced Prostate Cancer

  Biomedicines · 2026-04-22

  articleOpen access

  Background/Objectives: Combinations of PARP inhibitors (PARPi) and androgen receptor pathway inhibitors (ARPi) have led to clinical success in treating advanced prostate cancer. However, it is unclear where in the clinical paradigm these combinations will fare best, and their mechanism of action remains unclear. We sought to address open questions and explore alternative strategies to enhance PARPi efficacy. Methods: Viability and morphology were assessed in response to (1) abiraterone, olaparib, or combination and (2) enzalutamide, talazoparib, or combination in castration-resistant C4-2B cells and abiraterone- or enzalutamide-resistant derivative cell models (ARPi-resistant). The efficacy of the ATM inhibitor lartesertib with and without a PARPi was also determined. Western blots and RNA-sequencing were used to interrogate the mechanistic effects of treatment. Results: PARPi and ARPi combinations were effective in all models but provided the most benefit in ARPi-sensitive C4-2B cells. Mechanistically, ARPi was not found to affect homologous recombination repair gene expression but may increase PARP activity. Prolonged PARP inhibition was found to increase the expression of AR target genes, and PARPi pre-treatment increased sensitivity to enzalutamide. ATM inhibition significantly increases PARPi efficacy and appears to outperform ARPi-containing combinations in ARPi-resistant models. Conclusions: PARPi and ARPi combinations are effective in ARPi-resistant models, but efficacy appears stronger in ARPi-sensitive CRPC cells. Presented findings support a novel hypothesis that PARP inhibition may increase ARPi sensitivity with increasing AR activity. Additionally, ATM inhibition may provide more benefit than an ARPi in combination with a PARPi in ARPi-resistant settings. These findings support continued PARPi development for improving patient outcomes.

  PublisherDOI

• Figure S3 from PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells

  2026-03-16

  articleOpen accessSenior author

  <p>supplementary data</p>

  PublisherDOI

• Figure S5 from PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells

  2026-03-16

  articleOpen accessSenior author

  <p>Supplementary data</p>

  PublisherDOI

• IP62-10 TARGETING PLXND1 USING RNA BIOENGINEERING TECHNOLOGIES AND CUSTOMIZED LIPID NANOPARTICLES IN ADVANCED PROSTATE CANCER

  The Journal of Urology · 2026-04-27

  article
  PublisherDOI

• Aryl hydrocarbon receptor is critical for both AR-dependent and AR-indifferent enzalutamide resistance in castration-resistant prostate cancer

  Oncogene · 2026-03-23

  article
  PublisherDOI

• Figure S4 from PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells

  2026-03-16

  articleOpen accessSenior author

  <p>supplementary data</p>

  PublisherDOI

• Targeting NDUFS4 Disrupts Oxidative Phosphorylation and Induces Ferroptosis in Olaparib-Resistant Prostate Cancer

  Molecular Cancer Therapeutics · 2026-04-09

  articleOpen accessSenior author

  Resistance to PARP inhibitors (PARPi) remains a major challenge in the treatment of advanced prostate cancer. Although metabolic rewiring has been implicated in this process, the molecular drivers and therapeutic vulnerabilities underlying this adaptation remain poorly defined. We integrated transcriptomic, functional, and clinical analyses to identify mitochondrial regulators of PARPi resistance. RNA sequencing and gene set enrichment analysis revealed robust enrichment of oxidative phosphorylation pathways in PARPi-resistant prostate cancer cells, with consistent upregulation of NDUFS4, a nuclear-encoded subunit of electron transport chain complex I. Elevated NDUFS4 expression correlated with poor survival in patient cohorts from TCGA and SU2C/PCF. Functional analyses demonstrated that genetic knockdown of NDUFS4 impaired complex I activity, reduced mitochondrial mass, and re-sensitized resistant cells to olaparib. Pharmacologic targeting of NDUFS4 using the niclosamide analog ARVib-7 phenocopied genetic depletion, suppressing mitochondrial respiration and enhancing olaparib efficacy to inhibit the growth of resistant spheroids. Both NDUFS4 silencing and ARVib-7 treatment induced ferroptotic stress, as evidenced by intracellular iron accumulation and altered expression of ferroptosis-associated markers including COX2, CHAC1, NRF2, and GPX4. These findings identify NDUFS4 as a key mediator of PARPi resistance and a therapeutic vulnerability in advanced prostate cancer. Targeting NDUFS4 disrupts oxidative phosphorylation and induces ferroptosis, providing a strong rationale for combination strategies with PARP inhibitors to overcome drug resistance.

  PublisherOA PDFDOI

• Targeting Wnt/β-catenin and circadian regulator restores PRC2/EZH2-controlled chromatin bivalency and suppresses cell state diversity

  Journal of Clinical Investigation · 2026-03-17

  articleOpen access

  PRC2/EZH2 inhibitors (PRC2i/EZH2i) are promising for the treatment of advanced cancers including metastatic prostate cancer. Here, we show that PRC2i/EZH2i alone or in combination with androgen receptor (AR) inhibitors induced diverse cell state programs (CSPs) (e.g., response to stress or IFN, MYC targets, stem cells, EMT lineage plasticity, and multiple developmental programs), which led to increased tumor cell invasion, metastasis, and resistance to other drugs, in addition to modest suppression of tumor growth. In contrast to the current perception, our comprehensive, integrated genomics and epigenomics profiling of patient-derived xenografts (PDXs) and clinical tumors revealed that PRC2/EZH2 suppressed CSP genes by maintaining chromatin bivalency. Hyperactive Wnt/β-catenin signaling and inhibitors of polycomb-repressive complex 2/enhancer of zeste homolog 2 (PRC2/EZH2) and the AR alter chromatin bivalency through antagonism of PRC2 and stimulation of MLL2/KMT2B in a feed-forward manner. The circadian rhythm regulator REV-ERBα unexpectedly reprogrammed β-catenin in promoting bivalency resolution and CSP gene expression. Dual targeting of Wnt/β-catenin and EZH2 diminished diverse cell states by restoring bivalency and effectively blocked tumor growth. Our findings provide unexpected insights into chromatin bivalency and dysregulated circadian rhythms in the control of cell state diversity and identify alternative therapeutic strategies that target PRC2/EZH2 for advanced malignancies.

  PublisherDOI

• Abstract 3014: Targeting PLXND1 using RNA bioengineering technologies and customized lipid nanoparticles in advanced prostate cancer

  Cancer Research · 2026-04-03

  article

  Abstract Background: PLXND1 (Plexin D1) is a transmembrane receptor that plays critical roles in promoting neural lineage plasticity and driving resistance to enzalutamide therapy in prostate cancer. Despite its significance, PLXND1 has been considered "undruggable." siRNA-based therapeutics offer a strategy to silence disease-driving genes like PLXND1 but face limitations, including instability, poor cellular uptake, and off-target effects. Methods: We employed an RNA bioengineering approach using a tRNA/pre-miRNA-mir-34a scaffold to stabilize and express siRNAs targeting PLXND1 (BioRNA-siPLXND1). BioRNA/PLXND1-siRNA expression plasmids were constructed via molecular cloning, and the resulting BioRNA was purified and analyzed for quality, yield, and endotoxin levels. We tested BioRNA-siPLXND1 function in vitro and formulated it into lipid nanoparticles (LNPs) using two lipid components: DOPE and DOTAP. The stability, transfection efficiency, and safety of each formulation were evaluated in vitro and in vivo using prostate cancer cell lines and neuroendocrine prostate cancer (NEPC) patient-derived xenograft (PDX) organoids. Results: BioRNA-siPLXND1 achieved high yield and purity with low endotoxin levels. It efficiently silenced PLXND1 at the mRNA and protein levels, significantly inhibiting cell proliferation, colony formation, and organoid growth in vitro. Among the LNP formulations, LNP-DOTAP demonstrated higher transfection efficiency but greater cytotoxicity in normal cells, whereas LNP-DOPE showed a favorable safety profile and effective delivery. LNP-DOPE-loaded BioRNA-siPLXND1 remained stable for at least 7 days in vitro and suppressed tumor growth in NEPC PDX organoids. In vivo, LNP-DOPE accumulated in tumors within 2 hours, persisted for up to 4 days, and was predominantly retained in tumor tissue by day 7. Conclusions: Our study demonstrates the feasibility and therapeutic potential of a tRNA-based BioRNA platform for delivering PLXND1-targeting siRNAs in prostate cancer. LNP-DOPE serves as a safe and effective delivery system, offering a promising strategy for targeting "undruggable" oncogenes like PLXND1 in therapy-resistant prostate cancer. Financial support: This work was supported in part by grants from NIH/NCI R37CA249108 (Liu), R01CA251253 (Liu), R21CA277171 (Liu), Department of Defense HT9425-23-1-0144 (Liu), HT9425-23-1-0325 (Liu), HT9425-23-1-0324 (Dall’Era), and UC Davis Comprehensive Cancer Center Support Grant (CCSG) awarded by the National Cancer Institute (NCI P30CA093373). Citation Format: Huan Qu, Menghuan Tang, Qiufang Zong, Sohaib Mahri, Pengfei Xu, Joy C. Yang, Fan Wei, Junwei Zhao, Meijuan Tu, Neelu Bartra, Leyi Wang, Allen C. Gao, Kit Lam, Marc A. Dall'Era, Aiming Yu, Yuanpei Li, Chengfei Liu. Targeting PLXND1 using RNA bioengineering technologies and customized lipid nanoparticles in advanced prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3014.

  PublisherDOI

Recent grants

• NIH Grant R21CA179970

  NIH · $363k · 2016

• BLR&D Research Career Scientist Award

  NIH · 2020–2027

• NIH Grant R01CA109441

  NIH · $1.1M · 2012

• NIH Grant R01CA168601

  NIH · $1.5M · 2020

• Therapeutic targeting steroid sulfatase for advanced prostate cancer

  NIH · $2.0M · 2020–2026

Frequent coauthors

• Christopher P. Evans

  UC Davis Comprehensive Cancer Center

  297 shared

• Wei Lou

  294 shared

• Chengfei Liu

  University of California, Davis

  264 shared

• Joy C. Yang

  University of California, Davis

  156 shared

• Alan P. Lombard

  136 shared

• Nagalakshmi Nadiminty

  131 shared

• Shu Ning

  116 shared

• Cameron M. Armstrong

  University of California, Davis

  88 shared

Labs

• Urologic SurgeryPI

Education

• M.D., Urology

  University of California, Davis

  2000

• Ph.D., Molecular and Cellular Biology

  University of California, Davis

  1995

Awards & honors

• Ralph deVere White endowed Professorship in Urologic Oncolog…
• President, Society for Basic Urologic Research (SBUR), 2018,…
• Senior Research Career Scientist, Department of Veterans Aff…